How often do you prescribe testosterone replacement therapy (TRT) to your patients?

The answer to that question depends on your patients’ situation, of course. But a recent study presented at the American Urological Association’s annual meeting last May suggests that providers aren’t prescribing TRT as often as we might think.

The Study

Researchers led by Dr. Nelson Stone of Mount Sinai School of Medicine looked at data from 11,584 (mean age 61.6 years) men who underwent health assessments during Prostate Cancer Awareness Week in 2011 and 2012.

Testosterone levels were measured for about 42% of the men and considered in light of several variables, including age, race, fat in the diet, amount of exercise, weight, body mass index (BMI), diabetes, erectile dysfunction (ED), heart disease, and heart attack.

In this subgroup, almost 43% of the men had hypogonadism, defined as a testosterone level below 300 ng/dL.

Interestingly, only 3.9% of this group was on TRT.

TRT was more common among men with ED, those over age 65, and men with a BMI of 30 kg/m2.

In their abstract, the study team did not speculate on why so few hypogonadal participants were on TRT. But they encouraged healthcare providers to consider TRT for hypogonadal men, especially is they were diabetic, exercised infrequently, ate a high fat diet, or had a high BMI.

Common Conditions

Testosterone Controversy Continues

Last week, the U.S. Food and Drug Administration (FDA) announced two labeling changes now required for prescription testosterone products.

First, labels should clarify the approved uses of testosterone. Specifically, the FDA has approved testosterone therapy for the treatment of hypogonadism – low testosterone caused by medical conditions. This may include problems with the testes, pituitary gland, or other parts of the brain involved with testosterone production.

This change is prompted by concerns that physicians are prescribing therapy for men with age-related low testosterone, who do not have hypogonadism. “The benefits and safety of this use have not been established,” according to an FDA statement dated March 3, 2015.

Nevertheless, the FDA now requires testosterone manufacturers to include information about possible cardiovascular risks. It also requires manufacturers to conduct clinical trials to further investigate this potential link.

Testosterone Concerns

As a healthcare professional, you’ve no doubt heard the buzz about testosterone and “low T.”

It’s normal for men’s testosterone levels to decline as they age. This decline leaves some men feeling run down and depressed. They may lose interest in sex and develop erectile problems.

It may be easy to suggest that low testosterone is the culprit. Testosterone is widely marketed and often touted as an elixir that can return youth and vitality to the middle-aged man.

Certainly there are benefits to testosterone therapy. It can improve muscle power and bone mineral density. For some men, mood, libido, and erectile function get better as well.

But testosterone therapy is not appropriate for every man. If your patients are thinking about taking testosterone, several concerns should be addressed:

Testosterone therapy may not be needed. Symptoms such as fatigue, decreased sex drive, depression, and erectile dysfunction could very well signal testosterone deficiency. But these symptoms might be explained by other conditions, too. It’s important for patients to have a thorough examination before testosterone is prescribed. Also, some symptoms may be alleviated through lifestyle changes, like improved diet and exercise, making testosterone treatment unnecessary.

Testosterone therapy may have risks. At the end of January 2014, the U.S. Food and Drug Administration (FDA) announced its plans to investigate the safety of FDA-approved testosterone products. This decision came after two studies raised the agency’s concern. The first study, published in the Journal of the American Medical Association (JAMA) in November 2013, found increased risk of heart attack, stroke and death among men who took testosterone after coronary angiography. The second, which appeared two months later in PLOS One, found that heart attack risk increased for men aged 65 and older and for men younger than 65 with a history of heart disease. (Younger men with no history of heart disease were not at increased risk.)

Study funding may skew results, making them difficult to interpret. In a Medscape slideshow presentation, Dr. Charles Vega of the University of California, Irvine points out that half of the clinical trials examining cardiovascular events and testosterone have been sponsored by the pharmaceutical industry. In sponsored trials, the rate of cardiovascular events is 4%. In non-sponsored trials, the rate is 8%.

Men may try over-the-counter testosterone products, which can be risky. Some men feel embarrassed to discuss their symptoms with a physician, especially if they’re having sexual problems. They may see advertisements for testosterone products or hear about them from friends. Ordering such products online or picking them up at the drugstore may seem like a good way to avoid going to the doctor. But over-the-counter products are not always what they seem. They may include ingredients that aren’t listed on the label. These ingredients may cause dangerous interactions with drugs the man is already taking. Over-the-counter supplements are not regulated by the FDA. In the United States, testosterone is a controlled substance and illegal to sell without a prescription. (For more details on the risks of over-the-counter testosterone supplements, please click here.)

So who should take testosterone and how should therapy be managed?

Dr. Vega makes the following suggestions:

Only symptomatic men should be evaluated for possible [testosterone deficiency], and [testosterone deficiency] should not be diagnosed without 2 morning testosterone levels that are unequivocally low. Serum testosterone levels should be reevaluated 3-6 months after the initiation of testosterone treatment, with the goal of achieving serum testosterone levels in the mid-normal range. [Testosterone therapy] should be prescribed only for men who truly need it, and these men require close follow-up to ensure that treatment goals are met and to avoid overtreatment. Caution is warranted in recommending [testosterone therapy] to men at high [cardiovascular] risk.

Testosterone therapy can do a lot of good. But it’s important to consider it in full context.

Common Conditions

Testosterone Gel and BMI

If your patients or clients include older men, it’s likely that some have low testosterone (also called hypogonadism). Testosterone is an important hormone for men. It’s responsible for secondary sex characteristics like facial hair and a deepening voice. It also contributes much to a man’s sex life.

Testosterone levels naturally decline as men age. Some experts call this andropause and liken it to the estrogen decreases associated with female menopause, although this comparison is not entirely accurate. Testosterone declines for men tend to be more subtle than the estrogen declines in women.

Still, low testosterone can be troublesome. Men may feel fatigued and weak. They may lose muscle mass and gain body fat. And they often develop sexual problems, such as low sex drive and erectile dysfunction.

Some men replenish their testosterone through a prescription testosterone 2% gel. However, the effects of body mass index (BMI) on this type of therapy have not been widely studied.

New Research

In November 2013, the Journal of Sexual Medicine published a study by American researchers who examined the issue. They worked with 149 men between the ages of 18 and 75 who had baseline testosterone levels below 250/300 ng/dL. (According to the U.S. National Institutes of Health, a range of 300 – 1,000 ng/dL is considered normal.)

The men were divided into three groups based on their baseline BMIs. Tertile 1 included men with BMIs less than or equal to 29.1 kg/m2. The BMIs of men in Tertile 2 ranged from 29.2 to 32.4 kg/m2. Men in Tertile 3 had BMIs greater than 32.4 kg/m2). The mean ages for the men in Tertiles 1, 2, and 3 were 52.9, 54.0, and 54.2, respectively.

Each man used a testosterone 2% gel for 90 days. The gel was applied to the front and inner thigh. If needed, the dosage could be adjusted at specified points during the study.

After 90 days, the researchers found that 79.1% of the men in Tertile 1, 79.5% of the men in Tertile 2, and 73.8% of the men in Tertile 3 had testosterone levels in the normal range. Men with BMIs greater than 32.4 kg/m2 needed higher doses of testosterone to reach this goal, however.

The researchers found that the treatment was generally well tolerated, even for men who had increased doses. The most common adverse events were skin reactions, upper respiratory infections, and sinusitis.

Using Testosterone With Care

If you have a patient considering testosterone gel therapy, here are a few points to keep in mind:

· Therapy should be conducted under a doctor’s care. Only a qualified physician can determine the proper dose of testosterone for that individual patient. A doctor can also do a thorough examination to determine whether a man’s symptoms are indeed cause by low testosterone or whether other factors are involved.

· Men should be cautioned about over-the-counter testosterone supplements, which are widely marketed. Again, testosterone therapy should be done under a physician’s guidance. Over-the-counter preparations can be risky. (Click here to learn more about these risks.)

· Men using a testosterone gel should follow the doctor’s instructions carefully and read the accompanying medication guide. The application area should be covered to avoid transferring the gel to others, especially women and children. This guide, provided by the U.S. Food and Drug Administration, provides more information on the proper use of testosterone gel.

Common Conditions

PSA Test and Hypogonadism

Can a test used to screen for prostate cancer be used to confirm hypogonadism in men with sexual dysfunction? It’s possible, according to new research published in the Journal of Sexual Medicine in July 2013.

What is Hypogonadism?

Hypogonadism occurs when a man’s body doesn’t produce enough – or any - testosterone. The problem may stem from a problem with the testes, which produce the hormone. Or, it may result from problems in the brain, specifically the hypothalamus or pituitary gland, both of which play a role in testosterone production.

Testosterone is important to men’s health. It has a huge effect on sex drive and is involved with erectile function. It gives men their secondary sex characteristics, like facial hair and a deeper voice. It’s also involved with sperm production, strength, and muscle mass.

When men have hypogonadism, they often feel weaker, fatigued, and moody. Their sex drive decreases and they may have trouble getting erections. Their testicles may get smaller; their breasts may get larger. Low testosterone levels also put them at higher risk for osteoporosis.

It’s natural for men’s testosterone levels to gradually decline as they age. Testosterone therapy may help, but should be done under a doctor’s care.

What is the PSA Test?

PSA stands for prostate-specific antigen. Produced by the prostate gland, PSA is a protein that helps liquefy semen. The PSA test is a common, though controversial, screening tool for prostate cancer. A PSA reading above 4.0 ng/mL usually prompts more screening. However, such readings do not always indicate cancer.

What is the connection between PSA and Hypogonadism?

In this study, Italian researchers were interested in late onset hypogonadism. They noted that past research on the relationship between PSA and testosterone levels was “controversial” and set out to investigate whether PSA could be a useful marker for low testosterone in men with sexual problems.

Their study involved almost 3,000 men seeking treatment for sexual dysfunction. None of the men had had prostate disease before the study. Men with PSA levels above 4 ng/mL were excluded. The participants ranged in age from 18 to 85 years (mean age 52.5).

In addition to taking a variety of measurements, such as waist circumference, total testosterone, testis volume, blood pressure, and HDL cholesterol, the researchers interviewed the men and had them complete questionnaires designed to assess hypogonadism.

The researchers found that after adjusting for age, lower PSA levels were linked to conditions associated with hypogonadism, including delayed puberty, lower testis volume, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Men with lower PSA levels were also more likely to have problems with erections.

While these results did show that low PSA might help confirm a hypogonadism diagnosis, the study authors said the efficacy of PSA testing for this purpose was “modest.”

They explained that the relationship between PSA levels and testosterone was more evident when men’s testosterone levels were below average. The link was not as strong for men with normal testosterone levels. In the research, PSA levels did not rise when testosterone readings were above 8 nmol/L.

Also, the findings were more accurate in younger patients. When men are over a certain age, other factors are more likely to affect PSA. In these cases, using PSA to confirm hypogonadism could be less reliable.

With these points in mind, however, PSA testing could still help clinicians evaluate symptoms of hypogonadism in men with sexual dysfunction.

Causes - Low Testosterone

What are the symptoms/conditions of low testosterone?

Decreased testosterone causes a wide variety of clinical findings. The sexual manifestations of low testosterone include diminished sexual desire and sense of vitality as well as erectile dysfunction.

Additionally, men with low testosterone may experience decreased size or firmness of the testicles, breast enlargement and muscle loss. The growth of body hair usually slows, but the voice and size of the penis typically do not change. Hypogonadism also increases the risk of osteoporosis and fractures. Mental and emotional symptoms similar to those of menopause - mood swings, depression, irritability and fatigue may occur. When the onset is rapid, men can experience hot flashes.

Common Conditions

Treating Low Testosterone

What are the potential benefits of testosterone treatment?

Most studies of testosterone therapy have demonstrated an improvement in libido and sexual function in men with hypogonadism, or low levels of male hormones. Researchers have found that therapy increased sexual interest and increased the number of spontaneous erections. However, testosterone replacement may not improve erectile dysfunction if there are other causes of the condition.

In addition to its effect on sexual domains, testosterone replacement has been shown to benefit mood, reducing symptoms of depression, anger, fatigue and confusion. Other research suggests that treatment may have beneficial effects on bone mineral density. Further studies in these areas are needed.

In the U.S., several forms of testosterone replacement are approved for use. These include long- and short-acting injections, oral agents, patches and gels. Interest in these products has risen dramatically in the last decade or so.

Common Conditions

Diagnosing Low Testosterone

How are low testosterone levels diagnosed?

If a physician suspects low testosterone based on symptoms and physical examination, the diagnosis must be confirmed by laboratory testing.

Most circulating testosterone is bound to sex hormone-binding globulin and albumin. In young adult men, only about 2 percent of testosterone is unbound (free testosterone). Total testosterone (bound plus free testosterone) is the preferred measure since tests for free-testosterone are not as accurate.

Testosterone levels are best measured early in the morning. This is because testosterone level has a daily pattern (diurnal) where it is most abundant at about 8:00 a.m.

Testing of LH and FSH, other hormones that stimulate the testes, are also performed to determine whether the cause of low testosterone is primary or secondary.

Common Conditions

Overview - Low Testosterone

What is hypogonadism and the role of Testosterone?

Hypogonadism refers to reduced or absent secretion of testosterone. Testosterone is produced primarily by the testes. Testosterone plays an important role in the development and maintenance of many male physical characteristics such as sex drive, sperm production, muscle mass and strength, fat distribution and bone mass.

In primary hypogonadism, the testes themselves do not function properly. Secondary hypogonadism occurs if there are problems in the brain, (hypothalamus or pituitary gland), both of which play important roles in controlling the sex glands.

As a man ages, it is normal for testosterone levels to gradually decline. In America, approximately 2 million to 4 million American men have hypogonadism, but only about five percent currently receive treatment. In 2003, a large VA center survey suggests that the prevalence of men presenting with impaired libido and erectile dysfunction due to low testosterone may actually be much larger than previously thought.